DE69233258T2 - powder dispenser - Google Patents

Description

The present invention relates to generally devices that inhale a powder medication facilitate.

The uniformity or accuracy of a dose is a problem associated with known donors, who give a powder drug. In general, powder medications tend to to "pack up" into excessively large agglomerates, in particular if the size of the particles in the order of magnitude of a few micrometers. If the drug is in excessively large agglomerates given to a user, the large agglomerates tend to be on the Bouncing tissue in the back of the user's throat, and thus the Drug reaches the lungs of the user. Such an impact sometimes causes an uncomfortable "gagging" reflex or cough. It is also desirable the total dose delivered to a user is fully increased distribute to the inhalable portion and effectiveness of to maximize medication delivered to the user and those with large powder agglomerates linked To avoid accompanying problems.

US-A-4 046 146 (Rosskamp), US-A-4 811 731 (Newell), US-A-2 587 215 (Priestley) and US-A-4 524 769 (Wetterlin) each describe inhalers caused by the inhalation airflow operated by the user. One with user-operated dispensers linked Problem is that capital of the user to create an effective airflow a condition like bronchial asthma may be adversely affected can. It is believed that the Powder drug dispenser based on a user-generated airflow tend to be ineffective, especially if the Fortune of the user to generate an inhalation air flow by a Suffering adversely affected is. Another problem associated with user-operated donors is that different People's skills vary widely for generating inhalation air flows. Thus, the Requiring the user to generate a significant airflow for some users To cause complaints.

US-A-4,524,769 (Wetterlin) describes one Device similar to a TURBOHALTER T. M dispenser commonly used by Aktiebolaget Draco, Lund, Sweden is available and is said to be in Europe sold. This device has one perforated part with several Perforations for every dose of medication. The TURBOHALTER T. M. dispenser is one user-operated inhalation device and it is said that he would respond to the Suffering from problems with the above-mentioned user-operated drug dispensers connected are.

The field also has devices who inhale powdered medication by using Facilitating fuel delivery and distribution of the medication. Dispensers that use a fuel are described in WO 90/07351 and in Wetterlin US-A-4 534 345 and US-A-4 667 668.

• (a) einen Treibstoffbehälter und eine Treibstoffabgabeeinheit; und
• (b) eine Dosiereinheit zum Dosieren der pharmazeutisch aktiven Verbindung, dadurch gekennzeichnet, daß die Dosiereinheit zum Dosieren der pharmazeutisch aktiven Verbindung eine direkt mit einer Dosiereinheit verbundene Vorratskammer für die aktive Verbindung aufweist, wobei die Dosiereinheit eine perforierte Membran, die relativ zur Vorratskammer verschiebbar angeordnet ist, einen Halter für die perforierte Membran und eine Einrichtung zum Verschieben der Membran aufweist, wobei die Membran zwischen einer ersten Position, wo eine aktive Verbindung in die Perforationen in mindestens ei nem Teil der Membranfläche eingeführt wird, und einer zweiten Position verschiebbar angeordnet ist, wo dieser Teil der Membran in einen Treibstoffkanal eingeführt wird, der aus der Treibstoffabgabeeinheit heraus führt.

GB-A-2 144 997 describes a perforated membrane to be used in powder inhalers as a metering and holding device for a predetermined amount of a micronized, pharmaceutically active solid compound. In particular, the document describes to provide the following:

• (a) a fuel tank and a fuel delivery unit; and
• (b) a dosing unit for dosing the pharmaceutically active compound, characterized in that the dosing unit for dosing the pharmaceutically active compound has a storage chamber for the active compound which is connected directly to a dosing unit, the dosing unit having a perforated membrane which is arranged displaceably relative to the storage chamber has a holder for the perforated membrane and a device for displacing the membrane, the membrane being displaceably arranged between a first position, where an active connection is introduced into the perforations in at least part of the membrane surface, and a second position, where this part of the membrane is inserted into a fuel channel leading out of the fuel delivery unit.

Other prior art dispensers use chlorofluorocarbon, to deliver a pharmaceutically active compound. In these guys from donors, the drug is typical in the chlorofluorocarbon fuel suspended. While such donors with some success give a drug to a user is the use of chlorofluorocarbon fuels for reasons including Costs are not always desirable. Also means it that donor, like the ones mentioned above. complex to build, inefficient or difficult to use.

It is the task of the present Invention, an improved dry powder drug dispenser and to provide its use. This task comes with the appropriate claims Fulfills.

The present invention provides a simplified dry powder medication dispenser, which (1) effective and efficient use of a dry powder drug in the Inhales a user's inhalation airflow and distributes it there himself if this inhalation airflow has a speed that is slower is than the speed of an average person (2) allows highly efficient airflow within the dispenser, to dispense and distribute the dry powder medication, (3) very little Medicament wasted and (4) repeatable dosing accuracy provides.

According to one aspect of the present Invention is a dry powder drug dispenser for dispensing a Dose of powdered particles of a dry powder drug provided to a user's respiratory system. The donor has a housing and a device to a packed, predetermined, agglomerated Provide a dose of dry powder medication in a dosing chamber, which is dimensioned to the predetermined dose of dry powder medication contain. The dispenser also has an internal pressure generator to generate a pressure to the given dose in one powdered, deagglomerated, for inhalation therapy eject a suitable shape from the metering chamber and from the housing. The Donor has an effectiveness in deagglomerating the packed Dose, which is generally independent on the inhalation speed of the user.

The device preferably has a dosing element with surfaces that delimit the dosing chamber. The dosing chamber defines a loading axis that is generally perpendicular to the surfaces, that delimit one end of the dosing chamber. The facility for deployment a packed, predetermined, agglomerated dose preferably has a medication reservoir for storing a supply of dry powder medication and an agglomerator within the drug reservoir, a positive, directional To provide packing power to under a pressure sufficient to pack the dry powder into a reproducible dose that Dry powder medication from the medication reservoir into the dosing chamber to load.

The agglomerator is most preferred for movement over the Dosing chamber attached so that the positive direction-independent packing power has a component that is generally parallel to the loading axis. The Component of the packing force, which is generally parallel to the loading axis, gradually takes to when the agglomerator over moved at least part of the metering chamber.

The pressure generator preferably has a pressure chamber with a pressure outlet and a medication delivery channel on. The pressure chamber suddenly poses a substantial fluid pressure difference across the packed dose ready, so that Fluid flows around deagglomerate the packed dose into several inhalable particles. Stronger preferably the pressure generator provides a fluid flow at the dose, which initially generally has no speed, but it has a maximum Speed reached soon after the fluid started to flow Has. At the maximum speed, the fluid flow is turbulent and deagglomerates the packed dose into several inhalable ones Particle.

The pressure generator is also preferred a fluid pressure differential on gradually increasing portions of the dose. The pressure difference is most preferred by releasing a pressurized fluid generally immediately provided adjacent to the dose.

The dosing element, the medication reservoir, the discharge channel and pressure outlet are for relative movement between (1) a loading orientation, with the dosing chamber facing the drug reservoir is open, and (2) a dispensing orientation, the metering chamber between the pressure outlet and the discharge channel is arranged, attached. Between the loading and the delivery orientation gradually increases the dosing chamber, the drug delivery channel and the pressure outlet aligned.

The present invention also encompasses a use of the claimed donor for dispensing several single doses a dry powder medication, comprising the following steps: (1) Providing powdered particles of the drug within a housing, (2) packing the powdered particles into a predetermined agglomerated dose in a metering chamber, and (3) generating a fluid pressure to the predetermined dose by force from the dosing chamber and from the housing in one powdered, deagglomerated, for inhalation therapy eject suitable form.

A cartridge can be provided be which (1) for inclusion in and interaction with one Dry powder drug dispenser is suitable, the pressure generating and actuation mechanisms which are suitable for those required by a user Minimize or reduce inputs or manipulations; (2) after it is empty, in the dry powder drug dispenser another cartridge can be replaced; (3) reuse allowed the donor with a number of different cartridges; (4) may be constructed to tamper with the dry powder medication restrict and (5) optionally has a counter arrangement, which is an estimate the number of drug doses available in the cartridge.

The present invention is made with Further described with reference to the accompanying drawing, in which same reference numerals refer to the same parts in several views Respectively; show it:

1 a fragmentary perspective view of an embodiment of dispenser according to the present invention shown from the front;

2 a perspective view of the donor of 1 in a disassembled configuration rotated approximately 90 degrees and showing a piston for pressurizing the fluid pressure chamber;

3 to 5 enlarged sectional views of the device of the present invention taken approximately along lines 3-3 of FIG 1 with parts removed to show details and which sequentially represent the dispensing of a medicament to a user put;

5A to 5C enlarged fragmentary perspective views of parts of the donor of 1 which successively represent movement of a metering chamber in alignment with a pressure outlet channel;

5D an enlarged fragmentary schematic representation of an initial alignment of a metering chamber with the outlet channel, which during the in 5A to 5C sequence shown occurs;

6 a perspective view of portions of a metering element and a pressure generating element, which are preferably in the dispenser of 1 are included;

7 a perspective view of loading sheets on a support shaft, preferably in the dispenser of 1 are included;

7A a computer simulation which represents the movement sequence of a loading sheet relative to a dosing element;

8th a sectional view of a second embodiment of a dispenser according to the present invention;

9 a sectional view of a third embodiment of a dispenser according to the present invention;

10 a perspective view of a cartridge shown in disassembled arrangement;

11 an enlarged perspective view of a partially assembled cartridge;

12 an enlarged perspective view of some of the elements of the in 10 shown cartridge at an angle other than that of 10 to show various details;

13 a perspective view of the in 12 elements shown at an angle other than that of 12 to illustrate various details;

14 an enlarged perspective view of elements of the in 10 shown cartridge at a different angle to show details of portions of a counter assembly;

15 an enlarged perspective sectional view of the in 10 shown cartridge with assembled elements;

16 one too 15 similar enlarged perspective sectional view of the in 10 shown cartridge with parts omitted to show details;

17 another enlarged perspective sectional view of the in 10 shown cartridge with assembled elements and with a cover omitted to show details;

18 an enlarged sectional view of a cartridge, which from the in 10 elements shown are assembled, with elements removed and omitted to show details;

19 an enlarged sectional view of a cartridge, which from the in 10 shown elements is assembled and which has a sealing element between a metering sleeve and a pressure chamber; and

20 and 21 schematic representations of an example of a medicament dispenser for use with the cartridge, which successively illustrate the functioning of the cartridge in connection with the dispenser.

Now with reference to the 1 to 7 The drawing shows an embodiment of dispenser according to the present invention, generally designated by the reference number 10 is designated. The dry powder medication dispenser 10 gives a dose of powdered particles of a dry powder drug 12 to a user's respiratory system.

The donor 10 has an effectiveness in deagglomerating the packed dose, which is generally independent of the patient's inhalation rate. Thus, an inhalable amount of the dry powder medication can be delivered to a patient constantly, even at reduced speeds of the patient's inhalation airflow.

The dry powder medication dispenser 10 has a housing 14 on the optional mouthpiece section 15 having. The donor 10 has a device for providing a packed, predetermined, agglomerated dose of the dry powder medicament in a dosing chamber 32 which is sized to contain the predetermined dose of dry powder medication.

The device 10 preferably has a metering element 30 with surfaces on the dosing chamber 32 circumscribe. The dosing chamber 32 defines a loading axis f ( 3 ), which is generally perpendicular to the surfaces that form one end of the metering chamber 32 circumscribe.

The device for providing a packed, predetermined, agglomerated dose preferably has a medicament reservoir 11 for storing a supply of dry powder medication 12 and an agglomerator within the drug reservoir 11 to provide positive, multi-directional packing power to pressurize the dry powder 12 to pack into a reproducible dose, the dry powder drug 12 from the drug reservoir 11 into the dosing chamber 32 to load.

The agglomerator is most preferred for movement across the metering chamber 32 attached so that the positive, direction-independent packing force has a component that is generally parallel to the loading axis f. The component of the packing force, which is generally parallel to the loading axis f, gradually increases as the agglomerator moves over at least a portion of the metering chamber. The agglomerator is detailed below ter described.

The donor 10 also has an internal pressure generator 21 to generate a pressure to forcefully eject the specified dose from the dosing chamber 32 and out of the case 14 in a powdered, deagglomerated form suitable for inhalation therapy. Preferably, the pressure generator 21 a fluid pressure differential at gradually increasing portions of the dose. This feature is described in detail below. The pressure difference is preferably provided by releasing a pressurized fluid generally immediately adjacent to the dose. As used herein, the term "immediately adjacent to the dose" means that the donor 10 has essentially no obstacle or obstacle (e.g. one (relative to that of the generator 21 Provided pressure) a non-pressurized area of the ambient air or a tortuous or labyrinthine path) which may result in a pressure drop between the location of the release of the pressurized fluid and the dose, or which may otherwise cause the pressure to propagate from the generator to the dose.

The pressure generator also preferably provides 21 generally, immediately or suddenly, a substantial fluid pressure differential across the packed dose is ready so that the fluid flows to deagglomerate the packed dose into several inhalable particles. As used herein, when it is said that the pressure generator suddenly provides a fluid pressure differential across the packaged dose, it means that the donor has no obstacle to the pressure propagation from the pressure generator 21 would significantly delay or slow down the dose.

The powder medication 12 may belong to any suitable therapeutic category, such as, but not limited to, antibiotics, proteins / peptides, steroids, bronchodilators, anticholinergics, lipoxygenase inhibitors, PAF antagonists, potassium channel activators, mast cell stabilizers, bradykinin analogs, enkephalins or interleukin. For example, but not with the intent to limit, the powder can be leuprolide, albuterol, insulin, pirbuterol, beclomethasone, terbutaline, salmeterol, fluticasone, tiamcinolone, salbutamol, isoproterenol, epinephrine, fenoterol, formoterol, procaterol, pentamidine, pentamidine, pentamidine, pentamidine Oxitropium, budesonide or their pharmaceutically recognized salts.

The dry powder medication dispenser 10 is particularly suitable for delivering a given dose unit that has several very fine particles with an average diameter as small as about 0.3 micrometers or possibly even less. Generally, by "very fine" or "powdered" particles, an average particle diameter in a range from about 0.3 microns to about 20 microns, and preferably from about 0.5 microns to about 6.0 microns, is considered. For example, a dose of the powder drug 12 0.115 milligrams of solid powdered albuterol sulfate powder with an average particle size of approximately 3 microns.

The housing 14 preferably has an outer surface 8th and inner surfaces. These inner surfaces preferably have portions that delimit: (1) a metering element receiving chamber 9 , (2) the drug reservoir 11 , (3) a drug delivery channel 16 that is between an injection inlet end 17 (e.g. a circular opening with a diameter of 1.57 millimeters (0.062 inches) through a hole in the housing 14 is formed), which communicates with the metering element receiving chamber, and an outlet end 18 extends through the mouthpiece 15 leads through (4) at least one air inlet duct 19 with an inlet end through the outer surface 8th of the housing 14 passes, and an outlet end into the drug delivery channel 16 leads, (5) a fluid pressure chamber 22 and (6) a pressure outlet channel 23 with an inlet end that communicates with the fluid pressure chamber 22 communicates, and generally opposite the injection inlet end 17 of the drug delivery channel 16 located outlet end which passes through the inner surface which defines the metering element receiving chamber. The housing 14 may be constructed from any suitable metal or polymeric material, such as, but not limited to, polyacetal, polyethylene, polypropylene, polycarbonate, or combinations thereof.

The drug delivery channel 16 preferably has a cylindrical turbulent flow section 50 with a generally constant cross-section adjacent to the injection inlet end 17 is arranged to a substantially turbulent fluid flow from the fluid pressure chamber 22 to provide the dry powder drug 12 to distribute in the fluid. The drug delivery channel 16 optionally has a frustoconical laminar flow section 52 on that to the outlet end 18 of the drug delivery channel 16 borders and which widens in cross-sectional area towards this. The air entry holes 19 lead into the laminar flow section 52 to in the laminar flow section 52 to provide a laminar flow of fluid (preferably atmospheric air) and dry powder medication.

The inner surface sections that make up the laminar flow section 52 delimit, preferably diverge at an angle between about 15 and 30 degrees, preferably about 22 degrees. In the 1 to 5 shown embodiment of dispenser 10 has four circumferentially spaced, cylindrically shaped air entering holes 19 with axes generally transverse or normal to the axis of the drug delivery channel 16 lie.

The donor 10 has the movable chamber device or the metering element 30 which can be a cylindrical tubular member with an inside diameter of 8.46 millimeters (0.333 inches) and a wall thickness of 0.46 millimeters (0.018 inches). Alternatively, the dosing element 30 have a generally flat planar structure approximately 0.46 millimeters (0.018 inches) thick.

In a preferred embodiment, the metering element 30 a dosing part with an outer sealing surface 33 on and has surfaces that a metering chamber 32 limit, which has a longitudinal axis f and between spaced parts of the outer sealing surface 33 through the dosing element 30 extends through (see 3 to 5 ). The dosing chamber 32 receives a dose of a dry powder drug 12 , The volume of the dosing chamber 32 is dependent on a variety of factors, but is particularly dependent on the type of powder medication to be dispensed. If, for example, 0.115 mg albuterol sulfate from the dosing chamber 32 should be dispensed, the volume of the dosing chamber 32 approximately 0.24 cubic millimeters (1.45 x 10 (-5) cubic inches). If, also as an example, the dosing chamber 32 is cylindrical, the metering chamber can have a diameter of approximately 0.081 cm (0.032 inches) with a metering element 30 which is 0.046 cm (0.018 inch) thick.

The cross section of the dosing chamber shown 32 is circular to form a cylindrical channel. Alternatively, the dosing chamber 32 have any suitable shape, such as, but not limited to, triangular, square, star-shaped, hexagonal, arc-shaped, polygonal, or any suitable shape from combinations of straight and curved line segments. There is preferably a single metering chamber 32 which provides a constant dose intake volume that tends to take up constant volumes of a powder medicament, thereby contributing to repeatable dosing accuracy.

The cross section of the dosing chamber 32 can optionally be a little smaller than the cross section of the pressure outlet channel 23 to be a complete discharge of the drug 12 from the dosing chamber 32 to allow, and to ensure a perfect connection between the pressure outlet channel 23 and the dosing chamber 32 sure. If, for example, the cross section of the dosing chamber 32 circular with a diameter of approximately 0.81 millimeter (0.032 inch), then the cross section of the pressure outlet channel 23 also be circular with a diameter of approximately 1.32 millimeters (0.052 inches) or 1.40 millimeters (0.055 inches). Generally, the cross section of the injection inlet 17 for the drug delivery channel 16 approximately the same or a larger cross-sectional area than the cross-sectional area of the metering chamber 32 to have. For a circular cross section of the dosing chamber 32 with a diameter of approximately 0.81 millimeters (0.032 inches), the cross-sectional area of the injection inlet 17 also be circular with a diameter of approximately 1.57 millimeters (0.062 inches).

The dosing element 30 can be constructed from any suitable material, such as, but not limited to, polymer, plastic, or metal materials, or combinations thereof. That for building the dosing element 30 and the surfaces 9 Material used should be strong enough to pressurize a pressure chamber 22 to resist deformation. As best in the 5A - 5C and 6 can be seen is the dosing element 30 preferably adjacent portions of the inner surface 9 of the housing 14 attached, which form the dosing element receiving chamber. These sections of the inner surface 9 of the housing 14 which form the dosing element receiving chamber (see 6 ), can be a part 28 which also have portions of the fluid pressure chamber 22 forms. This preferably has at the gas pressure release opening 23 adjacent end of the part 28 a closed end to the pressure chamber 22 to build.

Devices such as elastomer seals (not shown) can be provided to provide a seal between the metering element 30 and the drug reservoir 11 to provide for powder leakage or leakage 12 from the re servoir 11 to prevent. Alternatively, the powder leak prevention device could be used 12 have a biasing device, such as a screw for clamping the metering element 30 in a fixed frictional engagement with that at the outlet 7 adjacent inner surface 9 of the housing 14 ,

The pressure generator preferably has 21 a pressure chamber 22 with a pressure outlet 23 and the drug delivery channel 16 on. The pressure generator 21 ( 2 ) is provided to hold fluid (e.g. ambient air) within the fluid pressure chamber 22 bring to a pressure above ambient pressure and around the fluid pressure within the fluid pressure chamber 22 to keep above the ambient pressure. The pressure outlet channel 23 can be through a cylindrical hole in the part 28 be educated. The part 28 can have a flange with an opening for receiving a screw 31 or any other suitable fastener to the part 28 by firmly attaching the part 28 on the housing 14 in a correct position relative to the injection inlet opening 17 to attach so that the part 28 a section of the inner surface 9 forms which delimits the metering element receiving chamber. Alternatively, the part 28 and the donor gene housing 14 have a one-piece element such as an integrally molded element.

An example of a section of the pressure generator 21 is in 2 as a piston or plunger 24 with an o-ring 29 and a pawl 25 shown, which is suitable to in a channel or a groove 26 in a fluid pressure element housing 27 to be included. An open end to the part 28 is suitable for receiving a luer fitting (not shown) or any suitable connector for an airtight connection between the fluid pressure element 20 and the part 28 to build.

The groove 26 in the housing 27 has a first section that is generally parallel to the axis of the fluid pressure element housing 27 extends, and a second closing portion 26 ' which extends generally perpendicular to the first section. To the fluid pressure chamber 22 putting pressure on a user covers the surfaces 33 of the dosing element 30 first the pressure outlet channel 23 tight ( 3 and 4 ) and then moves the piston 24 axially within the gas pressure element housing 27 to the housing 14 until the pawl is in the second closing section of the groove 26 ' attacks. The piston 24 can then go counterclockwise (relative to the housing 14 ) be rotated; around the pawl 25 in the second closing section of the groove 26 to move. The pressure inside the gas pressure chamber 22 tightens the piston 24 from the housing 27 away and force a frictional engagement between the pawl 25 and the closing portion of the groove 26 ' to the gas pressure inside the gas pressure chamber 22 to keep above the ambient pressure.

If also set up pressure generator 21 in 2 with a piston 24 it should be noted that the pressure generator 21 may have any suitable means for holding fluid (e.g., ambient air) within the fluid pressure chamber 22 bring to a pressure above ambient pressure and around the fluid pressure within the fluid pressure chamber 22 Maintain above ambient pressure, including, but not limited to, blowers, flexible bellows, or syringe / o-ring assemblies. Also, the means for locking the plunger in the pressure position may include any suitable means other than the pawl arrangement described.

The pressure generator 21 provides a fluid flow at the dose from a fluid which initially has no speed initially, but which reaches a maximum speed soon after. the fluid has started to flow. At maximum speed, the fluid flow is turbulent and deagglomerates the packed dose into several inhalable particles. The pressure and volume within the pressure chamber 22 by the generator 21 Should be provided should be sufficient to put the whole in the dosing chamber 32 loaded powder drug 12 to eject completely.

Without intending to follow a single theory, it is believed that the flow is from a pressurized pressure chamber 22 to the drug delivery channel 16 may be roughly similar to a flow through a nozzle or a restriction, so that there is a critical pressure within the pressure chamber 22 which gives a maximum speed of current within the drug delivery channel 16 provides. Any additional pressure above the critical pressure will not result in fluid velocities in the drug delivery channel 16 above the maximum speed.

It is believed that there is sufficient pressure and initial volume within the gas pressure chamber 22 ensure the maximum velocity of the fluid coming out of the pressure chamber 22 into the drug delivery channel 16 escapes. In general, the higher the speed of the fluid within the turbulent section 50 is, the greater the turbulence in the turbulent section 50 , The greater the turbulence, the more the donor spreads 10 the powder drug 12 into smaller, more inhalable particles. The turbulence has higher shear forces on the agglomerates of the drug 12 and causes collisions between the agglomerates of the powder drug, which helps to deagglomerate the large agglomerates into the desired primary particles. For example, the pressure of the fluid pressure chamber 22 to about 7.65 kg / cm ² (108.8 pounds per square inch) absolute.

For a given dosing chamber size 32 is the pressure of the fluid within the fluid pressure chamber 22 that is sufficient to remove the powder drug from the dosing chamber 32 ejected, controlled by several factors, such as the size of the pressure outlet channel 23 , the initial volume of the gas chamber 22 before pressurizing and the speed at which the dosing chamber 32 via the pressure outlet channel 23 is moved. For optimal delivery, it is generally assumed that a user uses the metering chamber 32 via the pressure outlet channel 23 should move as quickly as possible. Optionally, a biasing device such as a spring can be used around the metering chamber 32 via the pressure outlet 23 to move.

Finally, the entire cross-sectional area of the metering chamber preferably overlaps 32 with the pressure outlet 23 and the total time between the time when (1) the metering chamber 32 begins to get into the pressure outlet 23 open until (2) the entire cross-sectional area of the dosing chamber 32 with the pressure outlet 23 covered, disappears, is approximately four milliseconds.

If the pressure chamber 22 is under pressure, the drug delivery channel remains 16 on the ambient or atmospheric pressure and there is a possibility to put a pressure difference over the packed dose if the dosing chamber 32 begins to deal with the outlet 23 to cover up or get into the outlet 23 to open. An example of the pressure generator 21 which provides a substantial fluid pressure differential across the packed dose is that the pressure within the pressure chamber 22 at least approximately 1.1 times the ambient air pressure (the pressure in the drug delivery channel 16 ) should be. Preferably the pressure should be inside the pressure chamber 22 be at least twice the ambient air pressure. The volume of fluid under pressure within the chamber 22 should be sufficient to at least during the time between (1) the beginning of the opening of the dosing chamber 32 into the pressure outlet 23 and (2) covering the entire cross-sectional area of the metering chamber 32 with the pressure outlet 23 to provide a fluid flow.

A manually operated device 40 ( 1 and 2 ) or optionally an automatic device brings the dosing element 30 with at least parts of the outer sealing surface 33 in tight engagement with the inner surface surrounding the metering element receiving chamber 9 for a movement of (1) a loading position, the dosing chamber 32 generally with the outlet opening 7 of the drug reservoir 11 is aligned in (2) a dispensing position, the metering chamber 32 between the outlet end of the pressure outlet channel 23 and the injection inlet end 17 of the drug delivery channel 16 extends.

The metering element is preferably in direct connection with the reservoir. A direct connection means that the dosing chamber 32 is directly exposed to the reservoir without any filter or any number of small openings in between. In this way it is possible to optimally place the total amount of medicine in the chamber 32 to press.

The facility 40 can have an operation button 44 ( 1 and 2 ) with the dosing element 30 is functionally connected, and a fixed flange 37 to have. The housing 14 can have a fixed stop flange 38 to have. A turn of the knob 44 leads to movement of the flange 37 relative to the stop flange 38 , The stop flange 38 has surfaces that are suitable on the button flange 37 strike when the dosing element 30 is moved between the loading and the discharge position. A stop between one side of the stop flange 38 and the flange 37 ensures that the dosing chamber 32 in the correct dispensing position relative to the pressure outlet channel 23 and the injection inlet 17 moves, and a stop between the other side of the stop flange 38 and the flange 37 ensures that the dosing chamber 32 is in a position to the powder drug 12 from the reservoir 11 take.

In the loading position ( 3 ) seals the inner surface 9 which delimits the metering element receiving chamber, that of the medicament reservoir opening 7 opposite end of the dosing chamber 32 and the outer sealing surface 33 of the metering element part 32 closes the outlet end of the pressure outlet channel 23 tight. The sections 33 of the dosing element 30 close during an initial part of the movement of the metering element 30 from the loading position (e.g. 3 ) in the delivery position (e.g. 5 ) the outlet end of the pressure outlet channel 23 tight. During a final part of the movement from the loading position to the discharge position, gradually increasing sections of the pressure outlet channel move 23 , the dosing chamber 32 and the injection inlet 17 in alignment to a distribution of the dry powder drug 12 to allow.

If (1) the dosing element 30 is arranged in the loading position so that the drug 12 from the drug reservoir 11 into the dosing chamber 32 can move (2) the generator device 21 is actuated to fluid within the pressure chamber 22 pressurized, and (3) the metering element 30 then moved to the dispensing position while a user breathes air through the air inlet duct 19 inhaled, pressurized fluid flows out of the pressure chamber 22 through the pressure outlet channel 23 and empties the powder drug 12 from the dosing chamber 32 into the air flow inhaled by the user through the air inlet duct.

Although it has been described that the dosing chamber 32 relative to the housing 14 and the reservoir 11 moved, it should be noted that the metering element 32 or the drug reservoir 11 or the delivery channel 16 or the pressure outlet 23 can be attached for movement as long as (1) in the loading position or orientation of the dosing chamber 32 to the medication reservoir 11 is open and (2) in the dispensing position or orientation the metering chamber 32 between the pressure outlet 23 and the delivery channel 16 is arranged. Optionally, the delivery channel 16 be omitted.

5A . 5B and 5C successively illustrate sections of the pressure outlet channel 23 and the dosing chamber 32 that move in alignment with each other. 5D illustrates the dosing chamber 32 as it starts moving into the pressure outlet channel 23 to open.

If the dosing chamber 32 begins to get into the pressure outlet 23 to open, a pressure difference across the dose is provided. There is generally very little or no pressure loss between the location of the release of the pressurized fluid within the chamber 22 and the dose. The pressure difference from the pressure inside the pressure chamber 22 and the ambient pressure in the delivery channel 16 The maximum pressure difference is preferably provided via the Do sis, that can be provided for such pressures via the dose. Thus the pressure inside the pressure chamber 22 efficiently from the donor 10 used. Alternatively, the pressure provided by the generator can force the dose out of the metering chamber 32 ejects from a vacuum provided over the dose.

It is believed that the feature of the present invention is the pressure outlet channel 23 when dispensing the drug 12 directly on or directly adjacent to the dosing chamber 32 is arranged for complete distribution of the drug 12 inside the dosing chamber 32 contributes. It is believed that this "darkening" movement of the metering chamber 32 relative to the pressure outlet channel 23 while the pressure chamber 22 is under pressure, the powder in the dosing chamber 32 effectively removed and deagglomerated. It is believed that the dimming movement of the metering chamber relative to the pressure outlet allows for a complete, efficient distribution of the dry powder medication and provides a cloud of inhalable sized powder medication that is easily inhaled by a user, even with an inhalation airflow that is less than the speed, that an average person can inhale with.

It is believed that section P (see 5D ) the dosing chamber 32 that starts in the pressure outlet channel 23 and the injection inlet 17 opens from the dosing chamber 32 " under attack "with the remaining powder following shortly thereafter. The pressure is believed to be immediately at the location of the powder 12 the powder is effectively distributed and out of the dosing chamber 32 into the delivery channel 16 emits.

Dispensing a powder drug 12 in a manner according to the present invention reduces the amount required to completely dispense the powder 12 required amount of pressure. The pressure chamber 22 only needs to be pressurized to (1) the powder 12 to deagglomerate and (2) the drug 12 from the dosing chamber 32 out and into the drug delivery channel 16 to eject into it. It is not necessary for the pressure inside the pressure chamber 22 transfers all the powder into the user's mouth. Inhaling the user through the air intake holes 19 then pulls the dispersed powder completely through the drug delivery channel 16 and into the user's lungs.

Powder loading assembly

The dry powder 12 tends to stick to the walls of the drug reservoir 11 to adhere and form excessively large agglomerates. The donor 10 according to the present invention uses a new powder loading arrangement that contributes to constant dosing accuracy. The powder loading arrangement has a device for providing a packed, predetermined, agglomerated dose of the dry powder medicament in a dosing chamber 32 which is sized to contain the predetermined dose of dry powder medication. The device causes a transfer of the dry powder medication 12 from the drug reservoir 11 to the dosing chamber 32 in the dosing element 30 when the dosing element 30 is in the loading position.

The device for providing a packed, predetermined, agglomerated dose preferably has the medicament reservoir 11 and an agglomerator within the drug reservoir 11 to provide positive, location or directional packing power to the dry powder medication 12 under a pressure sufficient to dry powder 12 pack into a reproducible dose from the drug reservoir 11 into the dosing chamber 32 to load.

If the donor 10 is used to powdered particles of a dry powder drug 12 release, the powdered particles tend to flow from the drug reservoir 11 into the dosing chamber 32 to resist. The packing force is described as positive because it is independent of the ambient forces or greater than the surrounding forces, such as the Van der Waals forces between the powdered particles or the effect of gravity on the powdered particles. It is said that the packing force is independent of the direction, since the powder loading arrangement reproducibly the drug 12 into the dosing chamber 32 loads, even in an upside down or upside down orientation.

The effect of the packaging device of the present invention is to pack the powder medicament into the metering chamber. It is believed that packing the dosing chamber contributes to repeated, constant dosing accuracy since the chamber 32 is constantly packed with the same amount of powder.

The structure preferably has flexible loading blades 36 on, each having a proximal and distal end 39 and have a guide surface between the proximal and a distal end. The powder loading arrangement has at least one and preferably four flexible powder loading blades 36 on that on a shaft or a core 46 are attached, which is generally the same axis as the medicament reservoir 11 Has. An institution 40 ( 2 ) drives the leaves 36 over the surfaces of the drug reservoir 11 ,

The turning shaft 46 is powered by a powder loading button 47 turned. The leaves 36 are constructed of any suitable flexible material, including, but not limited to, polymers, metals, or polyesters. The rotation of the knob 47 while the dosing chamber 32 opens into the medication reservoir, causes the leaves to rotate 36 who the drug 12 of the Walls of the reservoir 11 scratches the dosing chamber at the same time 32 with a dose of the dry powder drug 12 loads and also helps the powder 12 stir to the powder 12 break into smaller agglomerates that are much easier into the dosing chamber 32 Loading.

The wave or the core 46 moves the flexible leaves 36 along a predetermined path within the drug reservoir 11 , with the guide surface leading and with the distal end 39 of the leaf 36 during a first section of the predetermined path ( 3 , solid line) moves along a portion of the inner surface that defines the drug reservoir 11 circumscribed. During a second section ( 3 , dashed lines) of the specified path, the distal end moves 39 of the leaf 36 along a portion of the outer sealing surface 33 of the dosing element 30 , which leads to a gradually increasing bending of the sheet 36 leads to form the guide surface into a convex surface and gradually the guide surface closer to the outer sealing surface 33 of the dosing element 30 to move.

When it is described that the distal end 39 of the leaf 36 Moved along a portion of the outer sealing surface of the metering element, it is considered here that a thin layer of powder 12 , e.g. B. 0.025 cm (0.01 inch) between the distal end of the leaf 36 and the dosing element 30 is available.

The drug reservoir 11 is generally cylindrical concave and has a drug reservoir axis that defines a reservoir radius R1. The outer surfaces of the dosing element 30 together with its axis define a radius R2. The core 46 holds the proximal ends of the leaves 36 for a rotary movement around the medication reservoir axis. The section of the outer sealing surface 33 of the dosing element 30 along which the distal end of the leaf 36 moved is cylindrically concave about an axis that is generally parallel to the drug reservoir axis R1.

The distance between the axis of the blade 36 / drug reservoir 11 and the axis of the dosing element 30 is less than the sum of the radii of the metering element 30 and the drug reservoir 11 (R1 + R2) to interlock the powder loading sheet 36 and the dosing element 30 to allow during the second section of the predetermined path so that in a direction that is generally the direction of the longitudinal or loading axis of the metering chamber 32 is the powder drug 12 into the dosing chamber 32 is loaded.

7A FIG. 5 illustrates a computer simulation of the powder loading assembly in accordance with the present invention. To create the computer simulation, it was assumed that a 0.025 cm (0.01 inch) layer of powder was between the sheet 36 and the dosing element 30 is available. The simulation illustrates the position of the leaf 36 for equal increments of core rotation 46 , If the flexible sheet 36 with the dosing element 30 is engaged, the leaf will 36 to bend. On the line of contact between the sheet 36 and the sealing surface of the metering element 30 (or a thin layer of powder directly adjacent to it 12 ) there is an imaginary sheet tangent line c, the tangent to the guiding surface of the sheet 36 and an imaginary tangent line d of the dosing element, the tangent to the outer sealing surface of the dosing element 30 is. The tangent line c of the sheet and the tangent line d of the metering element form a sheet tangent angle beta between them, which gradually decreases as the sheet is drawn 36 along the sealing surface and over the dosing chamber 32 emotional.

The loading arrangement according to the present invention helps to take the powder medication 12 advantageous in the dosing chamber 32 to pack. Right after the sheet 36 with the dosing element 30 has met, the movement is similar to a rolling movement. With movement of the leaf over the dosing chamber 32 The leaf tangent angle beta gradually decreases, so that the powder drug 12 in a direction generally along the loading axis f of the metering chamber 32 (e.g. in 3 through the dashed lines and in 7 shown) in the dosing chamber 32 is loaded. It is believed that forcing the powder medication in a direction generally along the axis f of the metering chamber 32 is, the chamber repeats with essentially equal amounts of the drug 12 loads, thereby contributing to the dosing accuracy. As an example, which is not meant to be a limitation, the metering element 30 have a radius R2 of about 0.475 cm (0.187 inches), the drug reservoir 11 can have a radius R1 of approximately 0.81 cm (0.32 inches) and the distance between the axis of the drug reservoir 11 and the axis of the dosing element 30 can be approximately 1.19 cm (0.47 inches). The powder loading sheets 36 can be a length from the axis of the drug reservoir 11 about 0.8 cm (0.315 inches) and are made of a flexible material such as polyester to ensure that the sheet is in the position shown in 3 is shown by the dashed lines.

Preferably has at least one of the loading blades 36 a scratching surface with a V-shaped notch ( 7 ) at its distal end 39 who have favourited Agglomerates of Dry Powder Drug 12 divided into smaller particles and the dry powder 12 from the walls of the drug reservoir 11 separates.

8th illustrates one generally with the reference numeral 60 designated second alternative embodiment of a dispenser according to the present invention, which has many parts, substantially the parts of the dispenser 10 are similar and are identified by the same reference number to which the suffix "A" is added.

In again 1 to 5 described donor 10 points in 8th donors shown 60 a housing 14A which is a drug reservoir 11A bounded, which for storing a powdered dry powder drug 12A is suitable, and a mouthpiece 15A on that has surfaces that have a drug delivery channel 16A with an injection inlet opening 17A and an outlet opening 18A to pass an inhalable dose of dry powder 12A limit for subsequent delivery to a user. A gas pressure chamber 22A which is suitable for being placed under a pressure above the ambient pressure, and a movable metering element 30A with surfaces that a dosing chamber 32A boundaries are also provided.

Different from the donor 10 points out the donor 60 arched air entry holes 62 arranged to at an angle relative to the axis of the channel that is much less than 90 degrees, preferably about zero (0) degrees, an air flow into the drug delivery channel 16A to provide in it. It is believed that the location arrangement of the in 8th air inlet holes shown 62 provides a laminar flow of air to a user.

9 illustrates one generally with the reference numeral 80 designated third alternative embodiment of a dispenser according to the present invention which has many parts which are essentially the parts of the dispenser 10 are similar and are identified by the same reference number to which the suffix "B" is added.

In again 1 to 5 described donor 10 points in 9 donors shown 80 a housing 14B on that's a drug reservoir 11B for storing a powdered dry powder medication 12B circumscribed; Air inlet holes 19B , a mouthpiece section 82 , a gas pressure chamber 22B which is suitable for being placed under a pressure above the ambient pressure, and a movable metering element 30B with surfaces that a dosing chamber 32B boundaries are also provided.

Different from the donor 10 point the inner surfaces of the dispenser 80 a drug delivery channel 84 with an injection inlet opening 85 and an outlet opening 86 to pass an inhalable dose of dry powder 12B for subsequent delivery to a user. The drug delivery channel 84 has a delay section 83 , which has a larger cross-sectional area than its turbulent and laminar flow sections and which is preferably designed hemispherical. The delay section allows rapid expansion and loss of the kinetic energy of the powder 12 after it's the dosing chamber 32b has left. The delay section 83 limits the passage of excessively large agglomerates of the drug 12 to prevent such agglomerates from being entrained in the back of the throat of the user. The hemispherical chamber 83 can have a radius between approximately 0.51 cm and 1.78 cm (0.2 inch and 0.7 inch) and can have a cylindrical channel 87 connected, which may have a radius between about 0.51 cm and 1.27 cm (0.2 inches and 0.5 inches).

functionality

Using the device of the present invention, one can devise a method of dispensing multiple individual doses of a dry powder drug 12 perform the following steps (1) providing powdered particles of the drug 12 inside a housing 14 , (2) packing the powdered particles 12 in a given, agglomerated dose in a dosing chamber 32 and (3) forcibly generating a fluid pressure from the dosing chamber at a predetermined dose in a powdered, deagglomerated form suitable for inhalation therapy 32 and out of the case 14 eject.

In particular, the functionality is now using the donor 10 explained as an example. First a user should see the dosing chamber 32 put it in a position where it holds the drug 12 from the reservoir 11 receives. The user can press the button 44 turn until the flange 37 on one side of the stop flange 38 strikes. This position is intended for the dosing chamber 32 in the in 3 position shown. In this position the user can push the button 47 turn to the leaves 36 to turn the powder drug 12 into the dosing chamber 32 to load.

Either before or after loading the dosing chamber 32 with the drug 12 should the gas pressure chamber 22 by pressing the piston 24 to the housing 14 and by turning the piston 24 to the pawl 25 in the groove 26 ' to move the pressure in the chamber 22 to be kept under pressure. During the chamber 22 is put under pressure, the dosing 30 be in any position, such as in 3 position shown or in the 4 position shown as long as the dosing chamber 32 not to the pressure outlet channel 23 and to the injection inlet 17 is open.

Once the dosing chamber 32 with the powder drug 12 is loaded and the pressure chamber 22 is under pressure, the user can then dispenser 10 by pressing the button as quickly as possible 44 turns until the flange 37 on the other side of the stop flange 38 strikes. This position is intended for the dosing chamber 32 in the in 5 position shown. If the powder-filled dosing chamber 32 begins to get into the pressure outlet channel 23 to open is the pressure inside the gas pressure chamber 22 strongly over the section of the metering chamber 32 concentrated, which is initially in the pressure outlet channel 23 ( 5D ) opens. It is believed that such a concentration of pressure at the location of the powder 12 the powder effectively from the dosing chamber 32 to the delivery channel 16 distributes and delivers.

Either immediately before, during or immediately after moving the dosing chamber 32 in the in 5 shown position, the user should inhale, allowing an air flow through the air inlet duct 19 and through sections of the drug delivery channel 16 generated. Inhalation is preferably generally in sync with the rotation of the button 44 to dispense the powder 12 to ensure to the user how to aim at the lungs. However, it is believed that some time may pass before inhalation without the donor becoming excessively ineffective. The pressure inside the gas pressure chamber 22 is generally not enough to get the powder 12 to be carried entirely into a user's mouth or nose, as would be appropriate to target the lungs. However, once the powder 12 from the dosing chamber 32 is expelled, a user should inhale deeply to the powder 12 effectively to the user’s lungs.

cartridge assembly

Now referring to 10 to 21 The drawing shows a preferred embodiment of a cartridge, generally designated by the reference number 100 is designated.

The cartridge 100 is in a dry powder drug dispenser 200 ( 20 and 21 ) added a mouthpiece section 201 and an actuator to be explained in more detail later 210 including a printing device 211 Has.

The cartridge 100 can be designed to be relatively inexpensive and disposable. Thus, when the drug is inside a cartridge 100 the cartridge is running low 100 replaced by another cartridge and the empty cartridge is thrown away. Such an arrangement allows the relatively expensive dispenser to be reused 200 with a number of different cartridges 100 ,

The cartridge 100 has a cartridge housing 114 with outer surfaces 119 on that is suitable in the dry powder dispenser 200 to be included. The housing 114 can be constructed from any suitable material that is used to build the housing 14 material used, and is preferably constructed from a material approved by the US Food and Drug Administration for medical purposes, such as polycarbonate grade # HP-1 Lexan ™, commonly available from General Electric of Pittsfield Massachusetts.

10 illustrates three individual main elements that are included in the assembly that make up the cartridge 100 forms. The main elements have a basic cartridge body BB, a central section AA and a cover CC. The parts AA, BB and CC can preferably be joined together by means of a press and / or snap lock to form parts of the cartridge 100 to build. In addition, the cover CC can be glued to the base body base BB in order to prevent unauthorized manipulation and access to the medicament within the cartridge 100 limit. It should be noted that, although the housing 114 has been described, preferably having three main parts AA, BB and CC, the housing 114 alternatively can consist of fewer or additional main parts.

The housing 114 has inner surfaces that a metering element receiving chamber 109 ( 19 ), a counter array receiving cavity 116 ( 18 ) and a medication reservoir 111 for storing a dry powder medication (e.g. the one described above in the description of the dispenser 10 described drug 12 ) exhibit. The medication voir 111 has a loading opening 101 ( 18 ) with the dosing element receiving chamber 109 communicates. As an example, which is not meant to be a limitation, the drug reservoir 111 be semi-cylindrical, as in 10 and 15 to 18 and may have an outer diameter of approximately 19.3 millimeters and a width of approximately 2.03 millimeters. A desiccant stopper 106 can be attached to the middle section AA to provide an access opening to the reservoir 111 to cover. The drying agent stopper 106 removes moisture from the drug 12 , It should be noted that the powder also starts through the opening 101 into the reservoir 111 can be loaded.

The inside surfaces of the case 114 also feature a drug release hole 115 (e.g., a cylindrical bore approximately 1.6 millimeters in diameter and approximately 3.2 millimeters in length) located between an outlet end 118 on the outer surfaces 119 of the cartridge housing 114 and an injection inlet end 117 extends that with the metering element receiving chamber 109 communicates. As in the 20 and 21 the outlet end is shown 118 with the mouthpiece section 201 of the drug dispenser 200 in connection. The drug release well also extends 115 as in the 12 . 13 and 19 is shown by sections of the two main parts AA and BB.

In addition, the inner surfaces of the housing 114 a pressure chamber 122 (e.g., a cylindrical chamber with a diameter of the interior surfaces of the chamber of about 5.82 Millimeters) on to the outer surfaces 119 of the housing 114 leads. The pressure chamber 122 is by, for example, a suitable one between the housing 114 and the donor 200 Pressed-in sealing device (e.g. an elastomer or rubber ring or a washer, not shown) functionally with the pressure device 211 of the drug dispenser 200 connected.

The pressure chamber 122 is from the printing device 211 of the drug dispenser 200 put under pressure. For example, the printing device 211 a piston / cylinder arrangement 211 , as in 20 and 21 shown. Alternatively, the printing device 211 have any suitable pressure means to pressurize fluid, such as, but not limited to, blowers or flexible bellows.

19 illustrates that the inner surfaces of the housing 114 generally opposite the injection inlet end 117 the drug well 115 a pressure release hole 123 (e.g., a cylindrical bore approximately 1.6 millimeters in diameter and approximately 1.01 millimeters in length) having a first end that mates with the pressure chamber 122 communicates, and has a second end that extends through the inner surface that the metering element receiving chamber 109 circumscribed.

The cartridge 100 has a metering element 130 on that inside the dosing element receiving chamber 109 is appropriate. The dosing element 130 has a cylindrical, tubular metering part 132 with sealing surfaces 133 and with a dosing chamber 131 on that through the dosing part 132 between spaced parts of the sealing surfaces 133 extends. The dosing element 130 can be built from a material that is used to build the metering element 30 The material used is similar, and is preferably a material that is approved by the US Food and Drug Administration for medical purposes, such as, but not limited to, variety # M90 SELCON ™, commonly available from HOECHST CELANESE.

The dosing chamber 131 takes a dose of dry powder medication from the medication reservoir 111 on. The volume of the dosing chamber 131 is dependent on a variety of factors that are similar to the factors that affect the volume of the metering chamber 32 Influence, especially the type of medication to be dispensed. As an example, which is not meant to be a limitation, the metering element 130 have a sleeve with dimensions similar to those in the example of the metering element described above 30 given are.

The cross section of the dosing chamber 131 can be similar to the cross section of the above-mentioned metering chamber 32 vary. There is preferably a single dosing chamber for providing a constant dose volume 131 which tends to ingest constant amounts of powdered medication to help ensure dosing accuracy.

As in the donor 10 can in the cartridge 100 optionally, a device such as elastomer or rubber seals (not shown) may be arranged to be generally at the opening 101 a seal between the dosing element 130 and the drug reservoir 111 provide.

Additionally shows 19 a sealing device that corresponds to the elements of the 10 shown cartridge 100 is added. The sealing device has, for example, a prestressed rubber or elastomer element 127 on that between the metering element 130 and the pressure release hole 123 / pressure chamber 122 is attached to a seal between the pressure release bore 123 / pressure chamber 122 and the dosing element 130 provide. The sealing device 127 can simultaneously with the remaining sections of the pressure chamber section 122 the housing can be injection molded or can be glued there with a suitable adhesive. As in 19 shown, the sealing device 127 a through hole so that the metering chamber 131 and the drug release well 115 with the pressure release hole 123 stay in contact.

The cartridge 100 also has an operating arm 112 on the one with the dosing part 132 is connected and has sections that extend over the outer surfaces 119 of the cartridge housing 114 extend out. The operating arm 112 has surfaces 110 on that are suitable from the actuator 210 of the drug dispenser 200 to be engaged. The operating arm 112 can be in any suitable manner, such as a snap lock pawl groove 108 , be connected to the metering element to ensure correct alignment of the arm 112 relative to the dosing element 130 provide.

The operating arm 112 moves the dosing element 130 from (1) a loading position (e.g. 21 ), the dosing chamber 131 to the loading opening of the medication reservoir 111 is open, in (2) a delivery position ( 20 ). The movement between the loading and the dispensing position of the dosing element 130 relative to the reservoir 111 , Injection inlet 117 and the pressure release hole 123 is the movement discussed above between the loading and unloading position of the metering element 30 relative to the reservoir 11 , the gas pressure release port 23 and the injection inlet 17 of in 3 . 5 and 5A to 5D shown donor 10 similar. As in the donor 10 seals in the cartridge 100 in the loading position, a portion of the inner surfaces that define the metering member receiving chamber 109 limit that the drug reservoir 111 opposite end of the dosing chamber 131 and a section of the sealing surfaces 133 of the dosing element 130 closes tight the second end of the pressure release hole 123 , The dosing chamber extends in the dispensing position 131 between the second end of the pressure release hole 123 and the injection inlet end 117 the drug release well 115 ,

During an initial portion of the metering element movement 130 from the loading position to the dispensing position, portions of the inner surface that close the metering element receiving chamber 109 delimit tightly both ends of the dosing chamber 131 and seal sections of the sealing surface 133 of the metering element part 132 tight the second end of the pressure release hole 123 , and during a last part of the movement of the metering element 130 Gradually increasing sections of the pressure release bore move from the loading to the dispensing position 123 , the dosing chamber 131 and the injection inlet 117 in alignment with each other.

If (1) the dosing element 130 is arranged in the loading position so that the powder medication 12 from the drug reservoir 111 into the dosing chamber 131 flows, (2) the pressure chamber is under pressure and (3) the dosing element 130 then moved from the loading position to the discharge position, pressurized gas is released from the pressure chamber 122 through the pressure release hole 123 pour and the powder drug 12 from the dosing chamber 131 into the drug release hole 115 discharged.

The cartridge arrangement 100 can optionally be one within the counter assembly receiving cavity 116 installed counter arrangement 140 to count the number of times the actuator arm 112 the dosing element 130 has moved from the loading position to the delivery position and back to the loading position. Such counting allows an estimate of the number of those in the medication reservoir 111 remaining doses of the drug.

The counter arrangement 140 has the operating arm 112 with a counter arrangement drive rod 141 , the cartridge housing 114 with a display device such as digits (not shown) on its outer surfaces, one within the counter array receiving cavity 116 attached bracket arrangement 142 with a ratchet pawl 143 on.

The counter arrangement also has the cartridge housing 114 with a ratchet hub 144 (e.g. on the bracket arrangement 142 arranged), a ratchet wheel 138 with one axis, axially centered hub bearing surfaces 145 and several teeth 146 on its scope. For example, the ratchet has 138 approximately 13.41 millimeters in diameter.

Each of the teeth 146 has a shoulder surface 147 and a detachment area 148 , The ratchet hub 144 is on the ratchet wheel bearing surfaces 145 axle bearing and the ratchet wheel 138 is inside the counter array receiving cavity 116 for rotation relative to the cartridge housing 114 appropriate. If the dosing element 130 Moved from the delivery position to the loading position, the drive rod engages 141 in a shoulder area 147 of the ratchet tooth 146 to the ratchet wheel 138 in a first direction of rotation 137 ( 10 ) relative to the cartridge housing 114 to register a drug dose delivery and the engagement between the pawl 143 and a shoulder surface 147 a ratchet tooth 146 stops the ratchet wheel from moving 138 relative to the cartridge housing 114 in an opposite direction to the first direction of rotation 137 when the drive rod 141 from engagement with the shoulder surface 147 and along a detachment surface 148 another ratchet tooth 146 moves when the dosing element 130 moved from the loading to the delivery position.

The counter arrangement 140 can only the ratchet described above 138 if, for example, there are only a few doses of a drug within the reservoir 111 are. In this example, the ratchet wheel 138 a pointing device, such as an arrow (not shown), for interaction with the digits (not shown) on the outer surface 119 the housing to count the number of times the operating arm 112 the dosing element 130 has moved from the loading position to the delivery position and back to the loading position. However, the counter arrangement preferably has a reduction device, in particular when the medicament reservoir 111 a large number of doses (e.g. over 25 ) contains.

The reduction device described below is intended to count up to approximately 210 Allow doses of a drug. The reduction device has the ratchet wheel 138 with an axially attached drive rod 150 and an eccentric rotating gear 151 on that one axis and suitable storage space 152 to hold the drive rod 150 and gear teeth running radially outward 153 Has. For example, the ratchet wheel 138 constructed of any suitable material such as polycarbonate or an acetal or an acetate, and has a rolling circle diameter of approximately 0.211 inches.

The reducer also has the inner surfaces of the cartridge housing 114 on that a ring 154 ( 14 ) with a ring axis and gear teeth running radially inwards 155 for engagement with the gear teeth 153 of the eccentric rotating gear 151 to have. For example, the rolling circle diameter of the ring 154 approximately 0.58 cm (0.23 inches).

If the ratchet 138 in the first direction 137 the teeth are gripping 153 of the eccentric rotating gear in the teeth 155 of the ring gear and the eccentric rotating gear 151 moves into a second spin direction 139 ( 10 ) generally opposite to the first direction of rotation 137 , Optionally, the reduction device has the eccentric rotating gear 151 with axially offset drive bearing slotted surfaces 156 and a cover plate 157 which a pointer device (e.g. the in 10 and 11 shown arrow) and a drive finger 158 has in the storage slot areas 156 of the eccentric rotating gear 151 is included. If the eccentric rotating gearwheel is in operation 151 relative to the ring 154 moves, move the storage slot surfaces 156 the cover plate 157 generally in the second direction of rotation 139 to thereby place the pointer device (e.g. the arrow) on the cover plate 157 relative to the display device (e.g. the digits not shown) on the outer surface 119 of the cartridge housing 114 to move.

The storage slot surfaces 156 are larger than the drive finger 158 and the drive finger can be inside the slot surfaces 156 move. In this way the cover plate transmits 157 the eccentric movement of the eccentric rotating gear 151 in increments of a generally circular movement so that the pointer device (e.g. the arrow) is on a defined, aesthetically pleasing circular path relative to the display device (e.g. the numbers) on the outer surfaces 119 of the cartridge housing 114 rotates.

The cartridge 100 also has a powder loading arrangement that is the powder loading arrangement for the dispenser described above 10 is similar. The cartridge 100 and the powder drawer arrangement allow the powder medication to be stored 12 in a reservoir 111 , which (1) can be stirred or shaken after the cartridge 100 has been delivered to the end user, and (2) separately from the donor prior to use 200 can be kept.

The powder loading assembly is a device for transferring a dry powder drug from the drug reservoir 111 to the dosing chamber 131 in the dosing element 130 when the dosing element 130 is in the loading position.

The powder loading arrangement has at least one and preferably a plurality of flexible blades 160 with proximal and distal ends. The leaves 160 For example, can be made from a polyetherimide material such as # 1000 ULTEM, commonly available from General Electric of Pittsfield, Massachusetts. Like the leaf 32 of the donor 10 separates the sheet 160 the agglomerates of the dry powder drug 12 into smaller agglomerates and separates the dry powder from the walls of the medication reservoir 111 ,

The powder loading assembly also has one with the blade 160 connected leaf wave 161 and a one-way or one-way gear clutch 162 on that with the leaf wave 161 is connected and is suitable from the actuator 210 of the drug dispenser 200 to be indented. For example, the actuator of the medication dispenser 200 an additional spring-loaded gear coupling 275 have, which in the unidirectional gear coupling 162 reaches for the leaf / leaves 160 to drive in a predetermined powder loading direction, and which is different from the one-way gear coupling 162 releases when the spring-loaded gear coupling 275 is rotated in a direction opposite to the powder loading direction.

If the sheet 160 in the cartridge 100 is attached within the drug reservoir and from the actuator 210 of the drug dispenser 200 the blade moves 160 , similar to the sheet 36 in the donor 10 , along the first and second predetermined path within the drug reservoir 111 , The guide surface of the blade guides during a first part of the predetermined path 160 and the distal end of the leaf 160 moves along a section of the inner surface that defines the drug reservoir 111 circumscribed. The distal end of the blade moves during a second portion of the predetermined path 160 along a portion of the outer sealing surface 133 of the dosing element 130 and touches it to gradually increasing the sheet 160 bend to shape the guide surface into a convex surface and gradually bring the guide surface closer to that of the metering chamber 131 adjacent section of the outer sealing surface 133 of the dosing element 130 to move a powder drug into the metering chamber 131 (please refer 7A ) to pack.

functionality the cartridge

The operation of the cartridge according to the present invention will now be with reference to the preferred embodiment 100 and with reference to an example of a donor 200 described. 20 and 21 illustrate the functioning of the cartridge one after the other 100 in connection with the donor 200 ,

In the 20 and 21 shown cartridge 100 is generally identical to that in 10 to 19 shown cartridge 100 , with the exception that in 20 and 21 the position of the operating arm 112 in the loading and unloading positions is generally lower than the position of the operating arm in 10 to 19 , The operating arm 112 is shown in this way to the operation of the actuator 210 of the donor 200 better to illustrate.

The cartridge 100 is in the donor 200 added which is a housing 202 with a mouthpiece section 201 , a printing device 211 and an actuator 210 having. The actuator is preferably a me mechanical arrangement that minimizes or reduces the inputs or manipulations required by a user. However, it should be noted that the invention is the cartridge 100 has and thus the actuator can have a number of different actuators, from the strictly manual actuation, similar to that with respect to the dispenser 10 described, up to the fully automatic actuating device or combinations of manual and automatic devices.

The actuator 210 for example, the in 20 and 21 shown actuator. This actuator has a cam fork member 204 (in 20 and 21 shown with dashed lines), the appropriate surfaces 206 has to the engaging surfaces 110 of the operating arm 112 take. The cam fork link 204 is rotatable on the housing 202 of the donor 200 attached to itself according to the positions of the operating arm 112 between a charging ( 21 ) and a delivery position ( 20 ) to move.

The actuator 210 has an arrangement of rack 220 and gear 221 on. The rack 220 has a button link 219 on that inside the guide surfaces of the housing 202 between one in 21 shown "ready to fire" position and one in 20 shown triggered position is manually displaceable. If the button link 219 is pushed into the ignition-ready position, the gear wheel rotates 221 in the clockwise direction in the drawing and causes a piston member in the pressure device 211 Fluid (e.g. air) within the pressure chamber 122 the cartridge is compressed. Alternatively, the rack 220 / button link 219 be replaced by a circular gear (not shown) connected to and driven by a rotatable mouthpiece cover (not shown).

The rotation of the gear 221 in 20 in a clockwise direction causes the gear 276 the spring drive clutch 275 rotates. The spring drive clutch 275 engages in the unidirectional gear coupling 162 to the leaves 160 within the drug reservoir 111 to drive in a predetermined powder loading direction and disengages from the unidirectional gear coupling 162 and does not drive them when the gear 221 in the counterclockwise direction in 20 rotates.

Generally at the same time as the button link 219 is pushed into the ready to fire position, causes a linkage 225 that the cam fork link 204 around its pivot point on the housing 202 against the preload of the release spring 226 rotates. The linkage 225 will cause the cam fork link 204 until shortly after the fork link engages 204 into the cam surfaces 231 on the jack link 230 rotates. The jack link 230 is rotatable on the housing for movement between a latched and released position 202 appropriate. The jack link 230 has a pawl spring 235 for pretensioning the pawl link 230 to the latched position and a release button 238 for manually turning the pawl link 230 against the bias of the spring 235 on.

If the cam fork link 204 into the cam surfaces 231 grips, the pawl member rotates 230 against the bias of the spring 235 from the path of the cam fork link 204 until a rear edge of the cam fork link 204 the cam surfaces 231 releases and then into the shoulder surfaces 239 the jack 230 attacks. This is the in 21 shown position of the cam fork member 204 and the jack 230 ,

The linkage 225 causes the operating arm 112 from the dispensing to the loading position before the button moves 219 fully moved to the ready to fire position. During a final section of the button's movement 219 in the ready to fire position, the operating arm 112 be in the dispensing position and the spring drive clutch 275 will cause the leaves 160 the dosing chamber 131 load with medication.

After the dosing chamber 131 loaded with a dose of medication and after the actuator arm 112 / cam fork member 204 in the in 21 position shown, the dispenser is ready to fire. To the donor 200 trigger, a user manually presses the button 238 which is the cam fork link 204 triggers which is under the bias of the spring 226 stands. The feather 226 moves the cam fork link 204 from the loading to the delivery position and consequently the actuating arm 112 from the loading to the delivery position. It should be noted that the jack link 230 need not be a button link, but instead may have a breath activated device, such as that disclosed in US Pat. No. 5,069,204; 4,664,107 breathable devices shown; and those mentioned in 4,664,107 including 3,187,784; 3,456,644; 3,645,645; 3,456,646; 3,565,070; 3,598,294; 3,814,297; 3,605,738; 3,732,864; 3,636,949; 3,789,843 and 3,187,784.

Now referring to 21 shows the linkage 225 a slider at its distal end. The linkage 225 can be constructed to after pressing the button 238 the gear 221 and the button 219 back to the in 20 shown position to move. Alternatively, the linkage 225 be constructed to yourself after pressing the button 238 to solve. Instead, the user can manually press the button 219 from the in 21 position shown in the in 20 move position shown after the cartridge 100 was triggered.

Claims (28)

Dry powder drug dispenser ( 10 ) to Dispensing a unit dose of a drug with: (A) a mouthpiece section ( 15 ) configured to be placed in a patient's mouth; (B) a movable chamber device ( 32 ) capable of receiving and holding an agglomerated mass of micronized particles of a drug having an average particle diameter of from about 0.3 microns to about 20 microns; (C) a pressurized chamber device ( 22 ) with an opening ( 23 ), which is arranged to be temporarily closed to the atmosphere, the pressurized chamber ( 22 ) is able to hold a supply of compressed air at least when the opening ( 23 ) is closed to the atmosphere; (D) the movable chamber device ( 32 ) is movable from a first medication-receiving position into a second medication-dispensing position, the movable chamber device () in the second position 32 ) directly at and next to the opening ( 23 ) is arranged; and (E) wherein the compressed air supply is immediately adjacent to the position of the movable chamber device ( 32 ) is when the movable chamber device ( 32 ) is in the second position, causing the donor ( 10 ) between the compressed air supply and the movable chamber device ( 32 ) has no air area that is not under pressure; where when the movable chamber means ( 32 ) in the second position, there is an immediate release of the compressed air to the agglomerated mass, whereby the agglomerated mass breaks down into the plurality of micronized particles in order to be released to the user. Donor ( 10 ), also with: a housing ( 14 ); means for providing a densely packed predetermined agglomerated dose of the dry powder medicament ( 12 ) in the chamber device ( 32 ); and an internal pressure generator ( 21 ) to generate a pressure to force the predetermined dose in a micronized, deagglomerated form suitable for inhalation therapy from the chamber device ( 32 ) and out of the housing ( 14 ) to eject. Donor ( 10 ) according to claim 2, wherein the pressure generator ( 21 ) suddenly provides a fluid pressure differential across the densely packed dose so that the fluid flows to deagglomerate the densely packed dose into a plurality of inhalable particles. Donor ( 10 ) according to claim 3, wherein the fluid pressure difference is a substantial fluid pressure difference. Donor ( 10 ) according to one of claims 2 to 4, wherein the pressure generator ( 21 ) a pressure chamber ( 22 ) to provide a first fluid pressure greater than ambient pressure, the dose is adjacent to the ambient pressure so that releasing the first pressure provides a pressure differential across the densely packed dose and provides a fluid stream that deagglomerates the dose, and wherein pressure difference provided by the dose is the maximum pressure difference that can be provided with the first pressure and the ambient pressure. Donor ( 10 ) according to one of claims 2 to 5, wherein the pressure generator ( 21 ) provides a fluid flow at the dose from a fluid that initially has no velocity, but that reaches a maximum velocity soon after the fluid begins to flow. Donor ( 10 ) according to one of claims 2 to 5, wherein the pressure generator ( 21 ) provides a fluid stream from a fluid that initially has no velocity, but then has a turbulent fluid stream of high speed relative to the tightly packed dose that deagglomerates the tightly packed dose into a plurality of inhalable particles. Donor ( 10 7) according to claim 7, wherein the high speed turbulent fluid flow is provided soon after the fluid begins to flow. Donor ( 10 ) according to one of claims 2 to 8, wherein the pressure generator ( 21 ) provides a fluid pressure differential across more and more portions of the dose. Donor ( 10 ) according to one of claims 2 to 8, wherein the pressure generator ( 21 ) generally provides a pressure differential across the dose by releasing a pressurized fluid immediately adjacent to the dose. Donor ( 10 ) according to one of the preceding claims, wherein the particle diameter is between 0.5 microns and 6 microns. Donor ( 10 ) according to one of claims 2 to 11, wherein the dispenser is a metering element ( 30 ) which has surfaces which the chamber device ( 32 ), the chamber device ( 32 ) has a longitudinal axis (f) and between spaced parts of an outer sealing surface ( 33 ) through the dosing element ( 30 ) extends through, and the device for providing a tightly packed predetermined agglomerated dose comprises: a medication reservoir ( 11 ) for storing the drug, and an agglomerator within the drug reservoir ( 11 ) to provide a positive directional compaction force to load the dry powder medication ( 12 ) from the medication reservoir ( 11 ) in the dosing chamber ( 32 ) under a pressure sufficient to pack the dry powder medication into a reproducible dose. Donor ( 10 ) according to claim 12, wherein the agglomerator for movement over the metering chamber ( 32 ) is attached so that the positive, direction-independent compression force has a component that is generally parallel to the longitudinal axis (f). Donor ( 10 ) according to claim 13, wherein that component of the compression force, which is generally parallel to the longitudinal axis (f), increases continuously as the agglomerator extends over at least a portion of the metering chamber ( 32 ) moved away. Donor ( 10 ) according to claim 14, wherein the agglomerator is a sheet ( 36 ) that bends more and more as it bends over the metering chamber ( 32 ) moved away. Donor ( 10 ) according to one of the preceding claims, wherein the performance of the donor ( 10 ) deagglomerating the densely packed dose is generally independent of the inhalation rate of the user. Donor ( 10 ) according to one of claims 1 to 16, wherein between the loading and the discharge orientation more and more sections of the metering chamber ( 32 ), the drug delivery channel ( 16 ) and the pressure outlet ( 23 ) move in a common direction. Use of the dry powder medicament dispenser according to one of the preceding claims for the delivery of a drug dose unit, with the following steps: (D) moving the movable chamber device ( 32 ) from a first medication-receiving position to a second medication-dispensing position, the movable chamber device ( 32 ) directly at and next to the opening ( 23 ) is arranged; where (E) the compressed air supply immediately next to the position of the movable chamber device ( 32 ) is when the movable chamber device ( 32 ) is in the second position, with the donor ( 10 ) between the compressed air supply and the movable chamber device ( 32 ) has no air area that is not under pressure; wherein there is an immediate release of the compressed air to the agglomerated mass, whereby the agglomerated mass breaks down into the plurality of micronized particles for delivery to the user. Use according to claim 18, further comprising: providing micronized particles of the medicament in a housing ( 14 ), Compressing the micronized particles into a predetermined agglomerated dose in the chamber device ( 32 ), and generating a fluid pressure to force the predetermined dose in a micronized, deagglomerated form suitable for inhalation therapy from the chamber device ( 32 ) and out of the housing ( 14 ) to eject. Use according to claim 19, wherein the step of Generation of a fluid pressure comprises the following step: sudden Generate a substantial fluid pressure differential across the tightly packed dose, resulting in a fluid flow, which deagglomerates the dose into a plurality of inhalable particles. Use according to claim 19, wherein the step of Generation of a fluid pressure comprises the following step: Produce a fluid stream, in addition to the tightly packed dose, of a fluid, which initially has no speed, so that the fluid flow then a reached maximum speed soon after the fluid started to flow Has. Use according to claim 19, wherein the step of Generation of a fluid pressure comprises the following step: Produce a fluid flow that is a high speed turbulent fluid flow relative to the densely packed dose that is the densely packed Dose deagglomerated into a plurality of inhalable particles. Use according to claim 22, wherein the turbulent High speed fluid flow is provided soon after to flow the fluid has begun. Use according to claim 19, wherein the step of providing micronized particles of the medicament ( 12 ) inside a housing ( 14 ) and the step of compacting the micronized particles into a predetermined agglomerated dose in a metering chamber ( 32 ) has the following steps: providing a dosing element ( 30 ) that has surfaces that the dosing chamber ( 32 ), the dosing chamber ( 32 ) has a longitudinal axis (f) and between spaced parts of an outer sealing surface ( 33 ) through the dosing element ( 30 ) extends through, and storing a supply of dry powder medication ( 12 ) in a medication reservoir ( 11 ), Using an agglomerator within the drug reservoir ( 11 ), which provides a positive, directional compaction force to the dry powder medication ( 12 ) from the medication reservoir under a pressure sufficient to compress the dry powder medication into a reproducible dose ( 11 ) into the dosing chamber ( 32 ) to load. Use according to claim 24, wherein the agglomerator extends over the metering chamber ( 32 ) moved away so that the positive directionally independent compression force has a component that is generally parallel to the longitudinal axis (f). Use according to claim 25, further comprising the step of continuously increasing that component of the compaction force which is generally parallel to the longitudinal axis (f) as the agglomerator extends over at least a portion of the metering chamber ( 32 ) moved away. Use according to claim 19, wherein the step of Generating a fluid pressure the step of releasing a fluid pressure generally immediately adjacent to the dose. Use according to claim 19, wherein the step of Generating a fluid pressure comprises the following steps: Provide a first pressure that is greater than the ambient pressure is Placing the dose next to the ambient pressure, release of the first pressure, a pressure difference across the densely packed dose provide away so that fluid stream to deagglomerate the dose, and where the over the Pressure difference provided dose is the maximum pressure difference that are provided at the first pressure and the ambient pressure can.